Run Detail

{"rows": [{"id":"a41f","significant":true,"mechanism":"Fluconazole inhibits CYP2C9, the main enzyme clearing S-warfarin","effect":"Rise in INR and bleeding risk within days of starting fluconazole","action":"Avoid the combination; if fluconazole is needed, switch to a non-interacting azole such as terbinafine for superficial infection, or if an azole is mandatory, reduce warfarin empirically and check INR in 2-3 days, then every 2-3 days until stable","numbers":["INR check at 2-3 days after starting fluconazole, then every 2-3 days until stable"],"note":"Even 150 mg weekly fluconazole for vaginal candidiasis is enough to cause this; the interaction persists for days after the last fluconazole dose because of its long half-life."},{"id":"7c02","significant":true,"mechanism":"Clarithromycin is a strong CYP3A4 and P-glycoprotein inhibitor, blocking simvastatin metabolism and transport","effect":"Markedly increased simvastatin exposure, causing myopathy and rhabdomyolysis with acute kidney injury","action":"Stop simvastatin during the clarithromycin course and for 2 weeks after; substitute azithromycin (no CYP3A4 inhibition) for the antibiotic, or switch the statin to pravastatin or rosuvastatin if an antibiotic change is not possible","numbers":["Hold simvastatin for the duration of clarithromycin plus 2 weeks after the last dose"],"note":"FDA labels this combination as contraindicated; the risk is highest in the first weeks of combined use and in older patients."},{"id":"b9d5","significant":true,"mechanism":"Linezolid is a reversible, non-selective monoamine oxidase inhibitor; sertraline blocks serotonin reuptake — additive serotonergic and sympathomimetic effect at the synapse","effect":"Serotonin syndrome (hyperthermia, clonus, rigidity, altered mental status, autonomic instability) and/or hypertensive crisis","action":"Do not co-prescribe; stop sertraline and allow a washout before starting linezolid, or choose an alternative antibiotic without MAOI activity (e.g., vancomycin, daptomycin, or a beta-lactam depending on the organism)","numbers":["Wash out sertraline for 5 half-lives (about 5 weeks) before starting linezolid if serotonin syndrome risk must be minimized; in practice, choose a non-MAOI antibiotic instead"],"note":"Linezolid's MAOI effect is weaker than older MAOIs but is still clinically relevant; the combination is listed as contraindicated or to-be-avoided in most references. Tedizolid has less MAOI activity but caution is still advised."},{"id":"3e18","significant":true,"mechanism":"Both drugs increase cGMP — sildenafil inhibits PDE5, nitrates stimulate guanylate cyclase — causing synergistic vasodilation","effect":"Severe, potentially fatal hypotension (syncope, myocardial ischemia, cardiovascular collapse)","action":"Contraindicated: never co-administer; if a patient on a nitrate takes sildenafil, do not give nitroglycerin for at least 24 hours after the last sildenafil dose (48 hours if the patient is older, has renal or hepatic impairment, or takes a CYP3A4 inhibitor)","numbers":["No nitrates for 24 hours after sildenafil (48 hours in older patients or with renal/hepatic impairment or CYP3A4 inhibitors)"],"note":"The prohibition runs both ways: a patient who has taken sildenafil within the past day should not receive nitroglycerin for chest pain in the emergency department."},{"id":"c6a7","significant":true,"mechanism":"Additive pharmacodynamic effect: spironolactone blocks aldosterone (reducing potassium excretion) and lisinopril blocks angiotensin II (reducing aldosterone and renal potassium excretion)","effect":"Hyperkalemia, which can cause muscle weakness, bradycardia, heart block, and fatal arrhythmia","action":"Avoid the combination if possible; if both are required (e.g., HFrEF with resistant hypertension), start low, check serum potassium and creatinine within 3-7 days of starting or dose-changing either drug, then at least every 3 months, and counsel the patient to avoid potassium supplements and salt substitutes","numbers":["Check potassium and creatinine at 3-7 days after starting or changing dose, then at least every 3 months"],"note":"Risk is highest in the first weeks after initiation or dose escalation and in patients with CKD, diabetes, or dehydration; the combination is evidence-based in HFrEF but requires structured monitoring."},{"id":"2f4b","significant":true,"mechanism":"Trimethoprim-sulfamethoxazole inhibits renal tubular secretion of methotrexate (via organic anion transporters and possibly reduced folate effects), and trimethoprim itself is a folate antagonist, impairing methotrexate clearance and adding antifolate toxicity","effect":"Severe methotrexate toxicity: myelosuppression (pancytopenia), mucositis, hepatotoxicity, acute kidney injury; can be fatal","action":"Avoid the combination; use an alternative antibiotic (e.g., a cephalosporin, nitrofurantoin for UTI, or a fluoroquinolone depending on the indication). If TMP-SMX is unavoidable, hold methotrexate for the antibiotic course and for 2 days after, give leucovorin rescue, and check CBC, creatinine, and methotrexate level urgently","numbers":["Hold methotrexate during the TMP-SMX course and for 2 days after; give leucovorin rescue"],"note":"Even short courses of TMP-SMX (e.g., 3 days for UTI) have caused fatal methotrexate toxicity, including in patients on low weekly doses; this is one of the most dangerous common drug interactions in outpatient practice."},{"id":"8d31","significant":true,"mechanism":"Omeprazole inhibits CYP2C19, the enzyme that converts clopidogrel to its active metabolite","effect":"Reduced active clopidogrel formation, diminished platelet inhibition, and increased risk of stent thrombosis and recurrent cardiovascular events","action":"Avoid omeprazole in patients on clopidogrel; use pantoprazole (minimal CYP2C19 inhibition) or an H2 blocker (e.g., famotidine) for acid suppression","numbers":[],"note":"The FDA warns against omeprazole with clopidogrel. The interaction is strongest with omeprazole and esomeprazole; pantoprazole is the preferred PPI. The clinical significance has been debated in large trials, but the mechanistic effect on platelet inhibition is real and guidelines recommend avoiding the combination."},{"id":"5a9e","significant":false,"mechanism":"none","effect":"none","action":"No change needed; pantoprazole has minimal CYP2C19 inhibition and does not meaningfully reduce clopidogrel activation","numbers":[],"note":"Pantoprazole is the preferred PPI in patients on clopidogrel. Some older observational data suggested a class effect, but pantoprazole is metabolized largely by CYP2C19-independent pathways and is the guideline-recommended choice."},{"id":"f072","significant":true,"mechanism":"Rifampin is a potent inducer of CYP3A4 and intestinal/hepatic enzymes and transporters (P-glycoprotein), accelerating ethinyl estradiol and progestin metabolism","effect":"Contraceptive failure: breakthrough bleeding and unintended pregnancy","action":"Use a non-hormonal or high-dose contraceptive method during rifampin therapy and for 4 weeks after stopping; if continuing hormonal contraception, use an alternative method (e.g., copper IUD or depot medroxyprogesterone, which is less affected) plus a barrier method, or add a barrier method throughout","numbers":["Continue backup contraception for 4 weeks after the last rifampin dose"],"note":"Rifampin is one of the few drugs for which enzyme induction is strong enough to reliably cause contraceptive failure; rifabutin (a weaker inducer) is the alternative rifamycin when an enzyme-inducing drug must be avoided."},{"id":"1b6c","significant":false,"mechanism":"none","effect":"none","action":"No change needed; amoxicillin does not induce or inhibit the enzymes that metabolize hormonal contraceptives","numbers":[],"note":"The long-standing belief that antibiotics reduce oral contraceptive efficacy is not supported for non-enzyme-inducing antibiotics. Only enzyme inducers (rifampin, rifabutin, griseofulvin, some anticonvulsants, St. John's wort) reliably cause failure. Counsel about backup contraception only if the illness itself causes vomiting or diarrhea that could impair absorption."},{"id":"e3f9","significant":true,"mechanism":"Amiodarone inhibits P-glycoprotein and CYP3A4/CYP2C9, reducing digoxin renal and non-renal clearance","effect":"Digoxin toxicity: nausea, vomiting, confusion, visual changes, bradycardia, heart block, and life-threatening arrhythmias","action":"When starting amiodarone in a patient on digoxin, reduce the digoxin dose by 50% and check a digoxin level 1 week after the change (and 1 week after any further dose change), targeting a trough of 0.5-0.9 ng/mL; monitor heart rate and renal function","numbers":["Reduce digoxin dose by 50% when amiodarone is started; check digoxin level at 1 week"],"note":"Amiodarone's inhibition develops over weeks because of its long half-life; the interaction persists for months after stopping amiodarone. Also monitor for additive bradycardia and AV block."},{"id":"94a2","significant":true,"mechanism":"Ibuprofen (an NSAID) inhibits prostaglandin-mediated afferent arteriolar vasodilation in the kidney, reducing lithium glomerular filtration and renal clearance","effect":"Rise in serum lithium concentration, causing lithium toxicity: tremor, ataxia, confusion, seizures, coma, and permanent kidney damage","action":"Avoid NSAIDs in patients on lithium; use acetaminophen or a non-NSAID analgesic for pain. If an NSAID is unavoidable, reduce the lithium dose by about 25-50% and check a lithium level in 5-7 days, then weekly until stable","numbers":["If an NSAID must be used, reduce lithium dose by 25-50% and check lithium level at 5-7 days, then weekly until stable"],"note":"The lithium level can rise within days of starting an NSAID and fall again when it is stopped; topical NSAIDs (e.g., diclofenac gel) have much less effect but are not entirely risk-free at high doses. Sulindac is sometimes cited as a less nephrotoxic NSAID but is still generally avoided."},{"id":"6d70","significant":true,"mechanism":"Allopurinol inhibits xanthine oxidase, the enzyme that inactivates azathioprine's active metabolite 6-mercaptopurine, causing accumulation of thiopurine metabolites","effect":"Severe, potentially fatal myelosuppression (leukopenia, thrombocytopenia, anemia) and increased infection risk","action":"Contraindicated combination: do not co-prescribe. If a patient on azathioprine needs a urate-lowering drug, use febuxostat (not metabolized by xanthine oxidase) or manage hyperuricemia with rasburicase/uricosurics as appropriate; alternatively, if allopurinol is essential, azathioprine must be stopped","numbers":[],"note":"If the combination is used despite warnings, azathioprine must be reduced to 25-33% of the usual dose with mandatory CBC monitoring — but the correct action is to avoid the combination entirely. Febuxostat carries its own cardiovascular caution but does not inhibit xanthine oxidase."},{"id":"0c85","significant":true,"mechanism":"Ciprofloxacin is a strong CYP1A2 inhibitor, blocking the metabolism of tizanidine (an alpha-2 agonist muscle relaxant)","effect":"Markedly increased tizanidine exposure causing profound hypotension, bradycardia, and excessive sedation","action":"Contraindicated: do not co-administer ciprofloxacin and tizanidine; choose an alternative antibiotic (e.g., a beta-lactam, azithromycin, or nitrofurantoin depending on the infection) or an alternative muscle relaxant (e.g., baclofen, cyclobenzaprine with caution)","numbers":[],"note":"The FDA labels this combination contraindicated; a single dose of ciprofloxacin can increase tizanidine AUC several-fold. Fluvoxamine is an even stronger CYP1A2 inhibitor and is also contraindicated with tizanidine."},{"id":"a7be","significant":true,"mechanism":"Carbamazepine is a potent inducer of CYP3A4 and P-glycoprotein, accelerating apixaban metabolism and transport","effect":"Reduced apixaban exposure, loss of anticoagulant effect, and increased risk of ischemic stroke or systemic embolism in atrial fibrillation, or recurrent venous thromboembolism","action":"Avoid the combination; if carbamazepine is required, switch the anticoagulant to warfarin (which can be managed with INR monitoring despite induction) or, if a DOAC is strongly preferred, use a DOAC less affected by induction — though all DOACs are affected to some degree. Alternatively, choose an alternative anticonvulsant with less enzyme induction (e.g., levetiracetam, lamotrigine, valproate)","numbers":[],"note":"Apixaban levels can fall by about 50% with strong CYP3A4/P-gp inducers. Warfarin is the practical alternative because INR monitoring allows dose adjustment despite induction. Valproate also inhibits some pathways but is not a strong inducer."},{"id":"d218","significant":true,"mechanism":"Clarithromycin is a strong CYP3A4 and P-glycoprotein inhibitor, blocking colchicine metabolism and transport (colchicine is a CYP3A4/P-gp substrate)","effect":"Colchicine toxicity: severe gastrointestinal toxicity, myelosuppression, rhabdomyolysis, neuromyopathy, multiorgan failure, and death — even at usual colchicine doses","action":"Avoid the combination; use azithromycin (no CYP3A4 inhibition) for the antibiotic. If clarithromycin is unavoidable, do not use colchicine; treat the acute gout flare with an NSAID (if no contraindication) or corticosteroids instead","numbers":[],"note":"Fatal colchicine toxicity has been reported with clarithromycin even with short courses and in patients with normal renal function. The interaction is so dangerous that the combination should be treated as contraindicated; colchicine dose reduction is not a safe workaround with strong CYP3A4 inhibitors."},{"id":"4f63","significant":true,"mechanism":"Ibuprofen binds to the same platelet COX-1 active site as aspirin and, when taken before aspirin, sterically blocks aspirin's irreversible acetylation of platelet COX-1 (pharmacodynamic antagonism); both also add GI and renal toxicity","effect":"Reduced cardioprotective antiplatelet effect of low-dose aspirin, potentially increasing cardiovascular events, plus additive GI bleeding and renal risk","action":"Separate the doses: take aspirin 81 mg at least 30 minutes before ibuprofen, or take ibuprofen at least 8 hours after aspirin; better, use acetaminophen for analgesia instead of ibuprofen in patients on aspirin for secondary prevention","numbers":["Take aspirin at least 30 minutes before ibuprofen, or ibuprofen at least 8 hours after aspirin"],"note":"The interaction is schedule-dependent: ibuprofen taken 2 hours before aspirin does not block aspirin's effect, but ibuprofen taken first does. COX-2-selective NSAIDs (e.g., celecoxib) do not block aspirin's antiplatelet effect but still add GI and renal risk. Acetaminophen is the preferred analgesic here."},{"id":"b5cd","significant":true,"mechanism":"Additive pharmacodynamic effect: sacubitril/valsartan (an ARNI containing valsartan, an angiotensin receptor blocker) plus lisinopril (an ACE inhibitor) causes dual blockade of the renin-angiotensin system, with additive hyperkalemia, hypotension, and renal impairment risk","effect":"Hyperkalemia, symptomatic hypotension, and worsening renal function; the combination also increases the risk of angioedema","action":"Contraindicated: do not co-administer an ACE inhibitor with sacubitril/valsartan. When switching from lisinopril to sacubitril/valsartan, stop lisinopril and allow a 36-hour washout before starting sacubitril/valsartan","numbers":["36-hour washout between stopping lisinopril and starting sacubitril/valsartan"],"note":"The 36-hour washout is required because sacubitril's active metabolite (LBQ657) inhibits neprilysin and, combined with an ACE inhibitor, markedly raises bradykinin and angioedema risk. This is an FDA boxed warning."},{"id":"27ea","significant":true,"mechanism":"Iodinated contrast can cause transient contrast-induced acute kidney injury; metformin is renally cleared and can accumulate if kidney function worsens, causing lactic acidosis (a pharmacodynamic/pharmacokinetic interaction via renal function)","effect":"Lactic acidosis (rare but potentially fatal) if metformin accumulates in the setting of contrast-induced kidney injury","action":"In patients with eGFR ≥60 mL/min/1.73m² and no other risk factors, continue metformin as usual. In patients with eGFR 30-59, or with liver disease, alcoholism, heart failure, or who will receive intra-arterial contrast, hold metformin at the time of the procedure and restart only after 48 hours if renal function is stable","numbers":["Hold metformin at the time of contrast administration and reassess renal function at 48 hours before restarting (for eGFR 30-59 or other risk factors)"],"note":"The FDA revised its guidance in 2016: metformin does not need to be stopped routinely before contrast in patients with normal kidney function. The risk is specifically lactic acidosis from metformin accumulation if contrast causes kidney injury."},{"id":"ec46","significant":true,"mechanism":"Phenelzine is an irreversible, non-selective monoamine oxidase inhibitor; pseudoephedrine is an indirect sympathomimetic that releases norepinephrine — the combination causes massive catecholamine release with no reuptake/inactivation brake","effect":"Hypertensive crisis (severe headache, intracranial hemorrhage, cardiac arrhythmia, death) from unopposed alpha-adrenergic vasoconstriction","action":"Contraindicated: patients on phenelzine must not take pseudoephedrine or any oral decongestant; counsel them to avoid all sympathomimetic amines (including phenylephrine, ephedrine, and amphetamines) and to check labels of cold remedies. Use non-sympathomimetic alternatives for congestion (e.g., intranasal saline, intranasal ipratropium, or an intranasal corticosteroid)","numbers":[],"note":"MAOIs also require dietary tyramine restriction, but the drug interaction with sympathomimetics is the most immediately life-threatening. Even small doses of pseudoephedrine (e.g., 30-60 mg) can precipitate a crisis. The interaction persists for 2 weeks after stopping phenelzine because MAO must be resynthesized."}]}